LPS または組織因子誘発ラット DIC モデルにおける血管作動性物質の動態の比較 Marked Difference in Plasma Levels of Vasoactive Substances between LPS-and Tissue-Factor-induced DIC Models in Rats





DICにおける多臓器不全 (MOF) の進展は, 多発した微小血栓による微小循環障害が主因と考えられてきた. この度, これに加えて, 血管作動性物質である一酸化窒素 (NO ; 代謝産物はNOX) およびエンドセリン (ET) がDIC病態に関連していないかどうかラットDICモデルを用いて検討した. Wistar系ラットを用いて, LPS誘発DICモデルはLPS50mg/kg, TF誘発DICモデルはTF3.75単位/kgを尾静脈より4時間かけ点滴静注し作成し, 血中D-dimer, NOX, ETを測定し, 腎糸球体フィブリン沈着 (GFD) を病理学的に検討した. LPS誘発DICモデルにおいては, 血中ETの有意な上昇, 腎糸球体フィブリン沈着は高度であったが, D-dimerの上昇は軽度であった. 一方, TF誘発DICモデルにおいては, 血中D-dimer, NOXの上昇は著明であったがフィブリン沈着はまったくみられなかった. 血管作動性物質は, LPSモデルにおいては臓器障害の進展 (ETによる微小循環障害) に, TFモデルにおいては臓器障害の阻止 (NOによる血流維持) に関連している可能性があり, 今後検討すべき点と思われた.

The multiple organ failure (MOF) in association with the disseminated intravascular coagulation syndrome (DIC) has long been thought to arise mainly from multiple microthrombi that disturb the microciruculation. In this report, we attempted to see whether or not shit hypothesis still holds true, and also to see whether vasoactive substances such as nitric oxide and its metabolites (NOX), and endothelin (ET) are involved in the development and propagation of DIC by utilizing animal DIC models induced in rats. Namely, the Wistar strain rats were intravenously infused either with 50 mg/kg of lipopolysaccharide (LPS) or 3.75 units/kg of tissue factor (TF) via the tail vein over a period of 4 hours, and the levels of D-dimer, NOX and ET in plasma were measured, and the kidney specimens were examined microscopically. In the LPS-induced DIC animalsm, a significant increase was noted in the plasma level of ET but not in the D-dimer, and marked fibrin deposition was observed in the renal glomeruli. On the other hand, marked increased in both the D-dimer and NOX in plasma were noted in the TF-induced DIC animals without any fibrin deposition in the renal glomeruli. Our data seem to indicate that involvement of vasoactive substances may vary in the development of MOF, i.e., ET disturbing the microcirculatin in the LPS-induced DIC, while NOX retaining the vascular integrity in the TF-induced DIC.


  • 日本血栓止血学会誌 = The Journal of Japanese Society on Thrombosis and Hemostasis

    日本血栓止血学会誌 = The Journal of Japanese Society on Thrombosis and Hemostasis 12(4), 273-279, 2001-08-01

    The Japanese Society on Thrombosis and Hemostasis

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